metric amounts of a base which was necessarily to activate the
C–H bond at the a-position of activated olefins in classical
methods.9
Notes and references
† Typical experimental procedure: to a solution of 1a (0.077 g, 0.5 mmol),
Pd(dba)2 (0.014 g, 5 mol%) and dppp (0.021 g, 10 mol%) in THF (2 ml) was
added 5a (0.129 ml, 1.2 mmol) and 6 (0.323 ml, 1.2 mmol) successively at
room temperature under an Ar atmosphere and the reaction mixture was
stirred for 6 h at that temperature. The reaction mixture was quenched with
water and then extracted with ether. The organic layer was dried over
MgSO4 and concentrated in vacuo. The resulting crude oil was treated with
ethyl acetate and a saturated KF solution. The mixture was stirred for 5 h
and then extracted with ether. The organic layer was washed with a
saturated NaCl solution, dried over MgSO4 and concentrated in vacuo. The
product 7a was isolated in 97% yield (0.097 g) by column chromatography
(silica gel, ethyl acetate+hexane = 1+10).
Scheme 3
1 P. Perlmutter, Conjugate Addition Reactions in Organic Synthesis,
Pergamon, Oxford, 1992; M. E. Jung, Comprehensive Organic Synthesis,
ed. B. M. Trost, I. Fleming and M. F. Semmelhack, Pergamon, Oxford,
1992, vol. 4, pp. 1–67; V. J. Lee, ref. 1b, pp. 69–137.
2 B. M. Trost and C.-J. Li, Tetrahedron Lett., 1993, 34, 2271; H.
Nakamura, J.-G. Shim and Y. Yamamoto, J. Am. Chem. Soc., 1997, 119,
8113; J.-G. Shim, H. Nakamura and Y. Yamamoto, J. Org. Chem., 1998,
63, 8470; H. Nakamura, H. Shibata and Y. Yamamoto, Tetrahedron Lett.,
2000, 41, 2911.
3 Except for this report, several methods are known for regioselective
carbon–carbon bond formation at the a-position of activated olefins: E. J.
Enholm and P. E. Whitely, Tetrahedron Lett., 1996, 37, 559; Y. Shvo and
A. H. I. Arisha, J. Org. Chem., 2001, 66, 4921.
4 Cu-catalysed carbon–carbon bond formation at the a-position of a,b-
unsaturated carbonyl compounds at 250 °C was reported: T. Tsuda, H.
Satoni, T. Hayashi and T. Saegusa, J. Org. Chem., 1987, 52, 439.
5 When other ester-based activated olefins, such as RCHNCHCO2Et and
RCHNC(CO2Et)2 were used, the desired products were not obtained and
the starting olefins were recovered quantitatively. Accordingly, a CN
group in two electron-withdrawing groups is required to accomplish the
present reaction. Complete coplanarity of two esters is difficult due to the
steric repulsion of electron-withdrawing groups although the small and
linear cyano group leads much less disruption than that of ester overlap.
This phenomenon is in accord with Boeckman’s and Shim and
Yamamoto’s previous results: R. K. Boeckmann and S. S. Ko, J. Am.
Chem. Soc., 1982, 104, 1033; J.-G. Shim and Y. Yamamoto, J. Org.
Chem., 1998, 63, 3067.
Next, we attempted the in situ generation of the Michael
acceptors followed by the palladium-catalysed regiospecific
carbon–carbon bond formation (all in one operation) (Scheme
4). This one-pot reaction proceeded smoothly in the presence of
H2O which was produced naturally by the condensation of
aldehyde and malononitrile. Benzaldehyde (13a) was treated
with malononitrile (14) in THF in the presence of tetra-
butylammonium fluoride (TBAF) (10 mol%) at rt for 1 h. After
14 was consumed completely, 5 mol% of palladium catalyst, 5a
and 6 were added successively. Upon completion of the
reaction, the mixture was extracted with ether and concentrated
in vacuo. After the treatment with a saturated KF solution, the
resulting oil gives the desired product 7a in 94% GLC yield
(90% isolated yield) by column chromatography. 4-Tolualde-
hyde (13b) also affords the desired product 7d in 94% GLC
yield by the same reaction conditions. In addition, 2-naph-
thaldehyde (13c) and trimethylacetaldehyde (13d) smoothly
underwent the condensation and subsequent palladium-cata-
lysed carbon–carbon bond formation to produce the desired
products 7e and 7f, respectively, in good yields.
6 Other palladium complexes, such as PdCl2(PPh3)2, Pd(PPh3)4, Pd(dba)2-
dppe also catalysed this reaction, however, the yield of 7a in these cases
were somewhat lower.
7 Replacement of 5a with other allyl sources resulted in the decrease of the
reaction speed and yield. These phenomena may be caused by the
differences of leaving group effect and transmetalation rate of allyl
sources.
8 Yamamoto and his coworkers have opened these types of chemistry,
hydrocarbonation of pronucleophiles with certain unactivated carbon–
carbon multiple bond in the absence of base: Y. Yamamoto and U.
Radhakrishnan, Chem. Soc. Rev., 1999, 28, 199 and references cited
therein.
9 According to the previous report, it was impossible to construct a new C–
C bond at the a-position of an activated olefin through the hydro-
carbonation of certain activated olefins with pronucleophiles in the
presence of a palladium complex: M. Meguro and Y. Yamamoto, J. Org.
Chem., 1999, 64, 694.
Scheme 4 Reagents and conditions: i, TBAF (10 mol%), THF, rt; ii,
Pd(dba)2 (5 mol%), dppp (10 mol%), 5a and 6.
In conclusion, we have developed the first transition metal-
catalysed hydrocarbonation8 of an activated olefin to give a new
carbon–carbon bond at the a-position. The present result seems
to be quite useful for the catalytic and regiospecific construction
of a new carbon–carbon bond at the a-position of Michael
acceptors in one operation and excludes the use of stoichio-
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